title: Activated Cdc42-bound IQGAP1 determines the cellular endocytic site.
abstract: Recruitment of specific molecules to a specific membrane site is essential for communication between specialized membranous organelles. In the present study, we identified IQGAP1 as a novel GDP-bound-Rab27a-interacting protein. We found that IQGAP1 interacts with GDP-bound Rab27a when it forms a complex with GTP-bound Cdc42. We also found that IQGAP1 regulates the endocytosis of insulin secretory membranes. Silencing of IQGAP1 inhibits both endocytosis and the glucose-induced redistribution of endocytic machinery, including Rab27a and its binding protein coronin 3. These processes can also be inhibited by disruption of the trimeric complex with dominant negative IQGAP1 and Cdc42. These results indicate that activation of Cdc42 in response to the insulin secretagogue glucose recruits endocytic machinery to IQGAP1 at the cell periphery and regulates endocytosis at this membrane site.
authors.affiliation: Department of Pharmacology, Oita University Faculty of Medicine, Hasama, Yufu, Oita, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kimura
authors.forename: Mami
authors.initials: M
authors.lastname: Yamaoka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takei
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ando
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iwamatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Niki
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004705:Endocytosis; D005947:Glucose / Q000502:physiology; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008840:Microfilament Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D021381:Protein Transport; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: C581598:Cdc42 protein, mouse; C101203:IQ motif containing GTPase activating protein 1; D007328:Insulin; D008840:Microfilament Proteins; D000075745:rab27 GTP-Binding Proteins; D020703:ras GTPase-Activating Proteins; C072061:coronin proteins; D006153:Guanosine Diphosphate; C512962:Rab27a protein, mouse; D020764:cdc42 GTP-Binding Protein; D020691:rab GTP-Binding Proteins; D005947:Glucose